The contribution of clinical subtype to survival differences among patients with de novo and recurrent metastatic breast cancer (dMBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
Danielle Marie File ◽  
Tomas Pascual ◽  
Allison Mary Deal ◽  
Amy Wheless ◽  
Elizabeth Claire Dees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
De Novo ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
Clinical Staging ◽  
Lower Grade ◽  
Significant Difference ◽  
Metastatic Sites

1030 Background: Patients with de novo metastatic breast cancer (dMBC) have superior median overall survival (mOS) compared to recurrent metastatic breast cancer (rMBC). Whether patient characteristics, prior treatment, tumor stage and innate biological differences contribute to this observation is unknown. Methods: Clinical and pathological data from patients diagnosed with MBC from 2011 to 2017 at the University of North Carolina (UNC) was obtained from the prospective UNC Metastatic Breast Cancer Clinical Database (223 dMBC, 607 rMBC). Only patients with known survival status were included. Subtype was determined by hormone receptor (HR) and HER2 staining of the primary tumor. Pathologic staging results were used when available, otherwise clinical staging was used. Patient and tumor characteristics were compared using chi-square testing, and survival outcomes by Cox proportional hazards modeling. Results: 26.9% of patients with MBC presented with dMBC, with significant variation in the ratio of dMBC to rMBC across subtypes. In particular, there were more cases of HER2+ dMBC than rMBC (26.9% vs 14.0%) and fewer cases of triple negative dMBC (20.6% vs 35.3%)(p-value < 0.001). Nearly half of all cases of HR-/HER2+ MBC were de novo (48.2%). dMBC was significantly associated with older age (p = 0.002), lower grade (p = 0.027), higher T and N stage (p < 0.001) and African American race (30% vs 22%, p = 0.022). There was no significant difference in proportion of patients with visceral metastatic disease or in number of metastatic sites at diagnosis. Median follow up was 39 months in both cohorts. mOS was 12 months greater in dMBC than rMBC (34m vs 22m, p < 0.001). These differences were significant across all subtypes except HR+/HER2+. The difference in mOS between dMBC and rMBC was greatest in the HR-/HER2+ subgroup (45m vs 15m, p = 0.006). In multivariable analysis, dMBC remained associated with improved survival (adjusted hazard ratio 0.59, p < 0.001) independent of variables including age, race, subtype, grade and number of metastatic sites at diagnosis. Conclusions: Patients with dMBC have significantly better prognosis than those with rMBC. This improved outcome is in part due to subtype variation, with more triple negative and fewer HER2+ tumors in rMBC, however these differences largely remained when stratified by subtype. In multivariable analysis, de novo presentation of MBC remained an independently significant contributor to longer survival. Further investigation should focus on biologic differences between dMBC and rMBC.

Survival among patients with untreated metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1095-1095
Author(s):  
Jennifer Kay Plichta ◽  
Samantha M. Thomas ◽  
Sarah Sammons ◽  
Susan G.R. McDuff ◽  
Gayle DiLalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
De Novo ◽  
Metastatic Breast ◽  
Disease Characteristics ◽  
Select Patient ◽  
Comorbidity Scores ◽  
Receive Treatment ◽  
Metastatic Sites

1095 Background: Treatments for metastatic breast cancer (MBC) have significantly improved survival for patients who receive treatment, yet data describing the prognosis for untreated patients is lacking. Therefore, we sought to assess the survival outcomes of patients with de novo MBC who did not receive treatment. Methods: Adults with MBC at diagnosis (clinical M1 or pathologic M1) were selected from the NCDB (2010-2016) and stratified based on receipt of treatment (treated = received at least one treatment; untreated = received no treatments). Differences between patient groups were tested using Chi-square tests for categorical variables and t-tests for continuous variables. Overall survival (OS) was estimated using the Kaplan-Meier method for the overall cohort and stratified by select patient and/or disease characteristics, and groups were compared with log-rank tests. Cox Proportional Hazards models were used to identify factors associated with OS in the untreated MBC subgroup. Results: Of the 53,240 patients with de novo MBC, the median age was 61y (IQR 52-71), and the majority had a comorbidity score of 0 (81.2%). Within this cohort, 49,040 (92.1%) received at least one treatment (treated) and 4,200 (7.9%) had no documented treatments (untreated). Untreated patients were more likely to be older (median 68y vs 61y, p < 0.001) and have higher comorbidity scores (p < 0.001). Patients with untreated MBC were more likely to have triple negative disease (17.8% vs 12.6%), and a higher disease burden (≥2 metastatic sites: 38.2% untreated vs 29.2% treated, p < 0.001). The median unadjusted OS in the untreated subgroup was 2.5mo vs 36.4mo in the treated subgroup (p < 0.001). For those who survived at least 1mo post-diagnosis, the median unadjusted OS in the untreated subgroup was 6.9mo vs 37.3mo in the treated subgroup (p < 0.001), which increased to 18.6mo and 40.3mo for those who survived at least 3mo post-diagnosis (p < 0.001). In the untreated population, unadjusted OS varied by breast cancer subtype (median 3.8mo for HR+/HER2-, vs 2.6mo for HER2+, vs 2.1mo for triple negative, p < 0.001) and number of metastatic sites (4.1mo for 1 site, vs 1.8mo for 2 sites, vs 1.1mo for 3 sites, vs 1.2mo for ≥4 sites, p < 0.001). After adjustment, variables associated with a worse OS in the untreated cohort included older age, higher comorbidity scores, higher tumor grade, and triple negative (vs HR+/HER2-) tumor subtype (all p < 0.05), while the number of metastatic sites was not associated with survival; these same findings were also noted when the analysis was limited to those who survived at least 1mo post-diagnosis. Conclusions: Patients with de novo MBC who do not receive treatment are more likely to be older, present with comorbid conditions, and have clinically aggressive disease. Similar to those who do receive treatment, survival in an untreated population is associated with select patient and disease characteristics. However, the prognosis for untreated MBC is dismal.

scholarly journals Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Simon Peter Gampenrieder ◽  
Gabriel Rinnerthaler ◽  
Christoph Tinchon ◽  
Andreas Petzer ◽  
Marija Balic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Triple Negative ◽  
Cox Regression ◽  
Tumor Therapy ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
World Population ◽  
Her2 Expression

Abstract Background About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody–drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). Patients and methods The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. Results As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74–1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68–1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. Conclusion Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

scholarly journals Prognostic factors and survival outcomes according to tumor subtype in patients with breast cancer lung metastases

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8298
Author(s):  
Siying Chen ◽  
Jin Yang ◽  
Yang Liu ◽  
Haisheng You ◽  
Yalin Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Cox Regression ◽  
Lung Metastases ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Metastatic Sites

Background Reports on the incidence and prognoses of lung metastases when diagnosing breast cancer patients with different subtypes are limited. Our study investigated the effect of molecular sub-typing stratification on the prognoses of lung metastatic breast caner patients. Methods Patients with breast cancer and lung metastases were identified from Surveillance, Epidemiology and End Results population-based data between 2010 and 2015. Univariate and multivariate Cox regression analyses were performed to identify risk factors and prognoses, overall survival (OS) and breast cancer-specific survival for patients with breast cancer lung metastases. Results We identified 6,516 patients with lung metastatic breast cancer, representing 1.7% of the entire cohort and 30.4% of the subset with metastatic disease. This included 2,940 hormone receptor (HR)+/HER2− patients, 852 HR+/HER2+ patients, 547 HR−/HER2+ patients and 983 triple-negative patients. The median OS for all lung metastatic patients was 13 months. Multivariate analysis revealed that those lung metastatic breast cancer patients of older age (>80), black race, with poorly differentiated tumors, carcinoma histology, triple-negative subtype, more metastatic sites and no surgery, and no chemotherapy showed significantly poor survival, both overall and breast cancer-specific. Conclusions Our findings show that molecular sub-type and more metastatic sites might have significant influence on the incidence and prognosis of breast cancer lung metastases. We also identified several prognostic factors that could guide therapy selection in the treatment of lung metastatic patients.

scholarly journals Clinical Outcomes of Metastatic Breast Cancer in Patients Having Both Pseudocirrhosis and Portal Hypertension with Evident Varices

2021 ◽  
Author(s):  
Wei-Li Ma ◽  
Dwan-Ying Chang ◽  
Ching-Hung Lin ◽  
Kao-Lang Liu ◽  
Po-Chin Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Cirrhosis ◽  
Metastatic Breast Cancer ◽  
Portal Hypertension ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
De Novo ◽  
Imaging Finding ◽  
Metastatic Breast ◽  
Her2 Positive

Abstract Background: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis–related complications such as portal hypertension (pHTN). This study compared the outcomes of metastatic breast cancer in patients with imaging-diagnosed pseudocirrhosis with or without pHTN. Methods: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Clinical pHTN was defined based on endoscopic evidence of esophageal or gastric varices. Results: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)–positive and human epidermal growth factor receptor 2 (HER2)–negative breast cancer. In total, 81 (76%) had initial metastases in both hepatic lobes, 91 (86%) had 4 or more liver metastases, and 32 (30%) had pHTN. The median overall survival (OS) was 5 and 13 months in patients with and without pHTN, respectively (p = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative breast cancer was 16, 9, and 2 months, respectively (p = .001). Patients with pHTN generally had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with pHTN had OS exceeding 1 year. In multivariate analysis, pHTN (p = .007) and triple-negative breast cancer (p = .013) were associated with poor OS. Conclusions: For patients with pseudocirrhosis, clinical pHTN was associated with liver cirrhosis–related complications and shorter median OS. A few patients with pHTN had prolonged OS with effective systemic treatment and aggressive supportive care.

scholarly journals Low Overall Survival in Women With De Novo Metastatic Breast Cancer: Does This Reflect Tumor Biology or a Lack of Access to Health Care?

2020 ◽  
pp. 679-687
Author(s):  
Leonardo R. Soares ◽  
Ruffo Freitas-Junior ◽  
Maria P. Curado ◽  
Regis R. Paulinelli ◽  
Edesio Martins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Access To Health Care ◽  
De Novo ◽  
Breast Surgery ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
Access To Health

PURPOSE As a result of its epidemiologic and therapeutic aspects, metastatic breast cancer (MBC) is a highly relevant clinical condition. This study aimed to estimate overall survival (OS) in women with de novo MBC in a Brazilian population. PATIENTS AND METHODS Patients were identified in the Goiânia population-based cancer registry between 1995 and 2011. All women with metastatic disease at diagnosis were included in the study. OS was analyzed at 5 and 10 years of follow-up. We used the Kaplan-Meier estimator and Cox regression for statistical analysis. RESULTS Over the 16-year period covered by the study, 5,289 women were diagnosed with breast cancer in Goiânia. Of these, 277 women (5.2%) had MBC. OS rates at 5 and 10 years were 19.9% and 7.3%, respectively. The mean OS time of women treated in the public health system was 7.5 months shorter than in women who had private health care (19.7 v 27.2 months, respectively). In the univariable analysis, the following factors were statistically significant for OS: T3/4 staging, histologic grade 3, progesterone receptor status, tumor phenotype, breast surgery, CNS metastasis at initial presentation, and surgery for resection of metastasis. In multivariable analysis, initial CNS metastasis (hazard ratio, 3.09; 95% CI, 1.16 to 8.19) and breast surgery (hazard ratio, 0.45; 95% CI, 0.25 to 0.78) remained independent prognostic factors. CONCLUSION OS was lower than rates found in specialist centers in Brazil and in developed countries. Several intrinsic and extrinsic factors were significant in predicting OS. Despite the difference in the 5-year survival rate, the type of access to health care was not significant in the multivariable analysis of the entire period.

scholarly journals Subdivision of M1 Stage for De Novo Metastatic Breast Cancer to Better Predict Prognosis and Response to Primary Tumor Surgery

2019 ◽  
Vol 17 (12) ◽  
pp. 1521-1528 ◽  
Author(s):  
Caijin Lin ◽  
Jiayi Wu ◽  
Shuning Ding ◽  
Chihwan Goh ◽  
Lisa Andriani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Competing Risks ◽  
Primary Tumor ◽  
De Novo ◽  
Metastatic Breast ◽  
Tumor Surgery ◽  
Competing Risks Model ◽  
Metastatic Sites

Background: Patients with de novo metastatic breast cancer (MBC) constitute a heterogeneous group with different clinicopathologic characteristics and survival outcomes. Despite controversy regarding its prognostic value, primary tumor surgery may improve survival for selected patients. Patients and Methods: Patients with de novo MBC were identified using the SEER database and were then divided randomly into training and validation sets. A Fine-Gray competing risks model was developed to identify the variables associated with increased cancer-specific mortality in the training set. The M1 subdivision system was established based on the independent prognostic factors. Cumulative incidence curves were estimated and compared using Gray’s test. Results: Involvement of brain or liver and number of metastatic sites were identified as independent prognostic factors in multivariate analysis. The M1 category was subdivided into 3 subcategories: M1a, single site involvement except brain and liver; M1b, liver involvement only, or multiple site involvement except brain and liver; and M1c, brain involvement regardless of number of metastatic sites, or liver and other sites involvement except brain (M1b vs M1a: subdistribution hazard ratio [SHR], 1.48; 95% CI, 1.29–1.68; M1c vs M1a: SHR, 2.45; 95% CI, 2.18–2.75). Patients with the M1a subtype benefited most from primary tumor surgery in the adjusted competing risks model (M1a: SHR, 0.57; 95% CI, 0.48–0.67, M1b: SHR, 0.62; 95% CI, 0.47–0.83, and M1c: SHR, 0.59; 95% CI, 0.44–0.80), whereas benefits conferred by treatment with chemotherapy alone increased with the upstaging of metastatic disease (M1a: SHR, 0.72; 95% CI, 0.62–0.83, M1b: SHR, 0.54; 95% CI, 0.44–0.68, and M1c: SHR, 0.53; 95% CI, 0.45–0.61). Conclusions: Subdivision of M1 stage facilitates prognosis prediction and treatment planning for patients with de novo MBC. Treatment offered should be decided in a coordinated multidisciplinary setting. Primary tumor surgery may play an important role in the management of selected patients.

BRAF: An emerging target for triple-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1099-1099 ◽  
Author(s):  
Joan Albanell ◽  
Julia Andrea Elvin ◽  
Siraj Mahamed Ali ◽  
Alexa Betzig Schrock ◽  
Jon Chung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Comprehensive Genomic Profiling ◽  
Er Positive ◽  
Cdh1 Mutation ◽  
Metastatic Sites ◽  
Erbb2 Amplification

1099 Background: A series of reports demonstrating the successful use of BRAF and MEK inhibitors in clinically advanced non-melanoma cancers has recently emerged. BRAF alterations in metastatic breast cancer (mBC) are rare and BRAF is not currently considered a target for the disease. Methods: DNA was extracted from 40 microns of FFPE sections from a series of 10,428 cases of metastatic breast cancer (mBC). Comprehensive genomic profiling (CGP) was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of > 550X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Results: 135 (1.2%) of the mBC featured alterations in BRAF. The median age of the 135 female patients was 66 years (range 27 to 83 years). The primary tumor was used for CGP in 50 (37%) and from metastatic sites including lymph nodes, liver, bone, lung, brain, adrenal and soft tissue in 85 (67%). Using CDH1 mutation as the definition of lobular mBC, 126 (93%) were ductal and 9 (7%) were lobular histology. Activating BRAF alterations included amplifications (48%), SV mutations (39%) and rearrangements (13%). No (0%) mBC had multiple BRAF GA in the same case. 34% of BRAF SV were V600E and 66% were a wide variety of non-V600E GA. 10 (7.4%) of 135 BRAF mutated mBC featured ERBB2 amplification with 1 (1%) having an ERBB2 SV mutation and 1 (1%) having both ERBB2 amplification and SV GA. Of the 115 BRAF GA cases with known hormone receptor status 71 (62%) were ER negative, 44 (38%) were ER positive and 63 (55%) were triple negative (TNBC). Other targetable genes enriched in mBC with BRAF GA included CDK6 (p = 0.001), HGF (p < 0.001) and MET(p < 0.001). The median TMB was 4.5 with 17 (13%) of cases with TMB > 10 mut/Mb and 7 (5%) of cases with > 20 mut/Mb. Conclusions: BRAF alterations, although uncommon in mBC representing only 1.2% of cases, are enriched in TNBC and feature both targetable base substitutions and rare fusions. BRAF GA may be a rare cause of anti-HER2 therapy resistance in a subset of ERBB2 driven mBC. Targetable genes co-altered with BRAF in mBC include CDK6, HGF and MET. The TMB in BRAF altered mBC is significantly higher than that for mBC in general and indicates potential role for immunotherapy for these patients.

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

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